摘要
目的:探讨大黄酚通过核因子E2相关因子2(Nrf2)/血红素氧合酶-1(HO-1)信号通路对糖尿病足溃疡大鼠新生血管生成及氧化应激的影响。方法:构建糖尿病足溃疡大鼠模型。将48只建模成功大鼠随机分为模型组、大黄酚组(给予30 mg/kg)、ML385组(Nrf2抑制剂,给予30 mg/kg)、大黄酚+ML385组(给予30 mg/kg大黄酚+30 mg/kg ML385),每组12只。另取12只大鼠作为对照组。各组给予相应药物干预4周。末次给药结束后24 h,测定创面愈合率,酶联免疫吸附法(ELISA)检测血清血管内皮生长因子(VEGF)、肿瘤坏死因子-α(TNF-α)以及创面组织碱性成纤维细胞生长因子(bFGF)、血管性血友病因子(vWF)水平;HE染色观察创面组织病理变化;检测血清中丙二醛(MDA)、超氧化物歧化酶(SOD)水平;蛋白免疫印迹法检测创面组织Nrf2、HO-1蛋白表达。结果:对照组创面组织中炎性细胞较少,成纤维细胞较多,可见丰富的毛细血管。与对照组比较,模型组创面组织中可见大量炎性细胞,新生毛细血管分布较少,创面愈合率、血清VEGF以及创面组织bFGF、vWF、SOD水平和Nrf2、HO-1蛋白表达降低,血清TNF-α、创面组织MDA水平升高(均P<0.05)。与模型组比较,大黄酚组创面组织中可见大量新生毛细血管,少量炎性细胞,创面愈合率、血清VEGF以及创面组织bFGF、vWF、SOD水平和Nrf2、HO-1蛋白表达升高,血清TNF-α、创面组织MDA水平降低(均P<0.05);ML385组创面组织中新生毛细血管显著减少,炎性细胞显著增多,创面愈合率、血清VEGF以及创面组织bFGF、vWF、SOD水平和Nrf2、HO-1蛋白表达降低,血清TNF-α、创面组织MDA水平升高(均P<0.05)。大黄酚+ML385组大鼠创面组织病理变化和上述指标介于大黄酚组与ML385组之间(均P<0.05)。结论:大黄酚能促进糖尿病足溃疡大鼠新生血管的生成,抑制炎症反应和氧化应激,其机制可能与激活Nrf2/HO-1信号通路有关。
Objective:To explore the effects of chrysophanol on neovascularization and oxidative stress in diabetic foot ulcers through nuclear factor E2 related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway.Methods:A diabetic foot ulcers rat model was established,and 48 rats successfully modeled were randomly divided into model group,chrysophanol group(treated with 30 mg/kg),ML385 group(Nrf2 inhibitor,treated with 30 mg/kg),chrysophanol+ML385 group(treated with 30 mg/kg chrysophanol+30 mg/kg ML385),with 12 rats in each group,and another 12 rats were selected as control group.Each group was given corresponding drug intervention for 4 weeks.24 hours after the last administration,the wound healing rate in each group was measured;serum levels of vascular endothelial growth factor(VEGF),tumor necrosis factor-α(TNF-α),wound tissue basic fibroblast growth factor(bFGF)and von willebrand factor(vWF)levels were determined by ELISA;the pathological changes of wound tissue were detected by HE staining;the serum levels of malondialdehyde(MDA)and superoxide dismutase(SOD)were detected;the Nrf2 and HO-1 protein expressions in wound tissue were detected by Western blot.Results:In the control group,there were fewer inflammatory cells,more fibroblasts and abundant capillaries in the wound tissue.Compared with control group,the model group had a large number of inflammatory cells could be seen in the wound tissue,and the distribution of new capillaries was less,the wound healing rate,serum VEGF,wound tissue bFGF,vWF,SOD levels,Nrf2 and HO-1 protein were significantly decreased,serum TNF-αand wound tissue MDA levels were significantly increased(all P<0.05).Compared with model group,the chrysophanol group had a large number of new capillaries and a small number of inflammatory cells in the wound tissue,and the wound healing rate,serum VEGF,wound tissue bFGF,vWF,SOD levels,Nrf2 and HO-1 protein were significantly increased,serum TNF-αand wound MDA levels were significantly decreased(all P<0.05);the ML385 group had new capillars in wound tissue were significantly reduced,and the inflammatory cells were significantly increased,and wound healing rate,serum VEGF,wound tissue bFGF,vWF,SOD levels,Nrf2 and HO-1 protein were significantly decreased,serum TNF-αand wound tissue MDA levels were significantly increased(all P<0.05).The pathological changes and the above indexes of the wound tissue in the chrysophanol+ML385 group were between the chrysophanol group and ML385 group(all P<0.05).Conclusion:Chrysophanol can promote the neovascularization and inhibit inflammatory response and oxidative stress in diabetic foot ulcers rats,the mechanism may be related to the activation of Nrf2/HO-1 signaling pathway.
作者
黎珊珊
区岛良
张梅
谢桃梅
LI Shanshan;OU Daoliang;ZHANG Mei;XIE Taomei(Department of Endocrinology,Danzhou People’s Hospital,Danzhou 571700,China)
出处
《陕西医学杂志》
CAS
2023年第12期1660-1664,共5页
Shaanxi Medical Journal
基金
海南省卫生健康行业科研项目(20A200537)。
